"Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell and antibody mediated immune processes." Wikipedia
Actually, there are two forms of Hashimoto's that are of concern in DS.
"Abnormal physiologic functioning affects thyroid metabolism and intestinal malabsorption. Frequent infections are presumably due to impaired immune responses, and the incidence of autoimmunity, including hypothyroidism and rare Hashimoto thyroiditis, is increased...
"Hashimoto's Thyroiditis is the autoimmune thyroid disease that is the most common cause of hypothyroidism, an underactive thyroid. A very rare condition associated with Hashimoto's Thyroiditis is Hashimoto's Encephalopathy, a neuroendocrine disorder. Much like the antibodies in Hashimoto's Thyroiditis attack the thyroid, in Hashimoto's Encephalopathy, antibodies attack neurons in the brain. While Hashimoto's Encephalopathy is quite rare (there may only be several dozen diagnosed patients in the U.S.) it is also likely that there are many more undiagnosed sufferers. Because it is little known and its symptoms are primarily neurological, it is easy to misdiagnosis or overlook and the symptoms frequently lead to mistaken neurological diagnoses.Continuing Research
"Some of the most common symptoms of Hashimoto's Encephalopathy include: disorientation, psychosis, tremors, concentration and memory problems, jerks in the muscles and lack of coordination, headaches, partial paralysis on the right side, and speech problems. Sometimes, patients are mistakenly diagnosed as having had a stroke, or having Alzeimer's. Typically, Hashimoto's antibodies levels will be high, and the patient may also have a diagnosable case of Hashimoto's Thyroiditis, but TSH levels may also be normal.
"The condition can also appear in adolescents, but is even more likely to be overlooked. The symptoms in adolescents, unlike adults, frequently include seizures, confusion and hallucinations. A drop in school performance is also a common symptom, along with progressive cognitive decline. Thyroid autoantibody levels should be evaluated in these adolescents with these symptoms, even when thyroid function tests are normal.
Priya Kishnani, MD and Gordon Worley, MD
Applicant’s Primary Department: Pediatrics
Title of Research:
Down Syndrome Disintegrative Disorder: Possible Hashimoto’s Encephalopathy?
Summary of Proposed Project:
The prevalence of autoimmune disease is much higher in Down Syndrome (DS) than in the general population. We have encountered 10 patients in the Duke DS Comprehensive Clinic who developed cognitive regression, autistic characteristics, and insomnia beginning in their early teenage years. These patients all had thyroid autoimmunity without clinical thyroid disease. Cognitive and developmental regression associated with thyroid autoimmunity has not previously been described in children with DS. We are naming this condition DS Disintegrative Disorder (DSDD), because of its similarity to Disintegrative Disorder in three to five year old typical children. Hashimoto’s Encephalopathy (HE) is an autoimmune CNS disease associated with but not caused by thyroid autoimmunity, most commonly reported in adults, but also reported to occur in some children. Cerebral folate deficiency is caused by either autoimmunity to a tissue folate receptor or by abnormalities of folic acid metabolism. In children, cerebral folate deficiency can also lead to autism, regression, and insomnia. Chromosome 21 contains many genes for folate metabolism, folate transport, and for enzymes that require folate for activity (including N6ANTI).
The purpose of the study is to characterize the clinical and laboratory findings in DSDD; evaluate thoroughly all patients with DSDD for known metabolic causes of regression; to test the hypotheses that antibodies to the tissue folate receptor and to alpha enolase are present in some subjects; and to evaluate subjects for evidence of abnormal folate metabolism.
Lay Summary of Proposed Project:
The prevalence of autoimmune disease is much higher in Down syndrome (DS) than in the general population. It appears that a subset of adolescent patients in the Duke Comprehensive DS Clinic have experienced significant regression. We would like to systematically evaluate these patients by review of medical records, laboratory evaluations, neuropsychological evaluations, and speech and language testing, and then compare the patients’ data to draw conclusions about their similarities. We are going to test these patients to see if they have a problem using folate correctly, and if they do, our next step in a future study is to treat the patients with folinic acid to see if their symptoms, such as learning, social withdrawal, perseverative thoughts, or trouble sleeping improve with treatment. Describing this subset of patients in the medical literature will help other clinicians caring for people with DS identify this dual diagnosis and monitor or treat these patients appropriately.